Stages of allergic reaction development
Immediate-type allergic reactions proceed in three consecutive stages, each with its own pathogenetic features.
- Immunological stage. Begins with the interaction of the incoming allergen with FcεRI receptors located on the mast cell membrane. This causes cross-linking of antibody-receptor complexes. This event generates an activation signal that enters the mast cell.
- Pathochemical stage. Characterized by mast cell degranulation. As a result, histamine and other biologically active substances stored in granules are released into the extracellular space. This is followed by the synthesis of eicosanoids.
- Pathophysiological stage. At this stage, surrounding tissue cells react: smooth muscle, vascular endothelium, nerve endings, mucous membranes, and glands. It is this tissue reaction that forms the visible clinical manifestations of allergy.
Systemic and local manifestations
The early phase of hypersensitivity starts within the first minutes after contact with the antigen and can resolve within an hour. Depending on the route of allergen entry and the site of the pathological process, systemic and local reactions are distinguished.
Systemic reactions include anaphylactic shock and urticaria:
- Anaphylactic shock is caused by severe vasodilation, increased vascular permeability, a drop in blood pressure, and smooth muscle spasm due to the action of histamine. In humans, it is often triggered by the administration of drugs or insect stings (in the presence of prior sensitization).
- Urticaria occurs when an allergen comes into contact with the mucous membranes or skin. It manifests as hyperemia, pruritic rash, and wheals.
Local reactions affect specific organs and tissues:
- In the bronchi, they cause smooth muscle spasm.
- On mucous membranes, they enhance mucus secretion.
- On the skin, they lead to the formation of rashes and wheals.
Characteristics of allergens
Allergens are a specific type of antigens capable of causing the degranulation of mast cells previously sensitized with IgE.
Most often, these are proteins or polypeptides with a molecular weight of 5 to 15 kDa. Interestingly, low-molecular-weight compounds (such as certain medications) can also become allergens. To do this, they must bind to the body's own proteins, acting as haptens.
The manifestation of allergenic properties is promoted by the following factors:
- Ability to penetrate tissue barriers.
- Presence of protease activity (typical for house dust mite allergens).
- Ability to bind lipids.
- Interaction with high-affinity FcεRI receptors ensuring cross-linking of IgE molecules.
- Entry of the allergen specifically through mucous membranes or in small doses.
Classification and nomenclature
A single ideal classification of allergens has not yet been created, so they are grouped according to various criteria.
By origin:
- Animal (insect venom, animal dander, Dermatophagoides dust mites).
- Plant (birch and ragweed pollen).
- Microbial.
- Synthetic.
By route of entry:
- Inhalant (entering via the respiratory tract).
- Food.
- Injectable.
Drug allergens are considered separately; they can be of natural or synthetic origin.
To designate plant and animal allergens, a strict nomenclature is used: the first three letters of the genus name are taken, followed by the first lowercase letter of the species and a serial number. For example, Amb a 1 is the first allergen of ragweed (Ambrosia artemisiifolia).
Induction of the allergic response
The basis of allergy development is a Th2-dependent humoral immune response leading to IgE synthesis. This is a mandatory condition: an allergic reaction occurs only upon re-exposure to the allergen when the body is already sensitized.
The formation of such a response upon first exposure to the allergen is promoted by:
- Specific microenvironment of dendritic cells in mucous membranes.
- The effect of interleukin-10 (IL-10) produced by mast cells.
- The absence of classical inflammatory stimuli that normally direct dendritic cell development along the DC1 pathway.
Briefly: answers to topical questions
What inflammatory mediators are released during mast cell degranulation?
During mast cell degranulation, preformed factors from granules and de novo synthesized mediators are released.
Preformed substances include:
- Vasoactive amines — histamine and serotonin.
- Proteoglycans — heparin, chondroitin sulfates A and C.
- Proteases — tryptases, chymases, carboxypeptidase A.
- Enzymes — peroxidase, RNase, histidine decarboxylase, dehydrogenase.
- Chemotactic factors — eosinophil and neutrophil chemotactic factors.
Newly synthesized mediators include:
- Eicosanoids — leukotrienes (LTC4, LTD4) and prostaglandins (PGD2).
- Cytokines — IL-5, IL-6, TNFα, GM-CSF.
- Platelet-activating factor (PAF).
Which cytokines are produced by Th2 cells to stimulate IgE synthesis by B cells?
To stimulate IgE synthesis by B lymphocytes, Th2 cells produce the interleukins IL-4 and IL-13.
- Interleukin-4 (IL-4) is the primary isotype switch factor that highly specifically induces Cε gene selection and switches antibody synthesis to the IgE class.
- Interleukin-13 (IL-13) acts at the post-transcriptional level, further stimulating IgE production.
These cytokines ensure B lymphocyte activation and their differentiation into plasma cells producing specific IgE antibodies.
What are the types of hypersensitivity reactions according to the Gell and Coombs classification?
According to the classification by P. Gell and R. Coombs, there are four types of hypersensitivity reactions, differing in the mechanism of tissue damage:
| Type | Name | Mediators and mechanism |
|---|---|---|
| I | Anaphylactic | Mediated by IgE (less commonly IgG4), causing mast cell degranulation. |
| II | Cytotoxic | Mediated by IgG and IgM antibodies, causing complement-dependent cytolysis of target cells. |
| III | Immune complex-mediated | Mediated by soluble immune complexes (IgG, IgM) causing tissue damage. |
| IV | Cell-mediated (delayed-type hypersensitivity) | Mediated by specific interaction of sensitized T lymphocytes with the antigen. |
Which specific low-molecular-weight compounds most commonly act as haptens in the development of allergies?
The sources do not specify which compounds act as haptens "most commonly." They provide the following examples of haptens or low-molecular-weight substances that acquire immunogenicity after binding to proteins:
- Drugs and their metabolites — halothane; medicinal products in general.
- Ethylene oxide.
- Haptens causing contact dermatitis — dinitrochlorobenzene, dinitrophenol, p-phenylenediamine, neomycin.
- Metals — nickel.
- Other low-molecular-weight compounds — foreign peptides, DNA, lipids, and low-molecular-weight organic compounds.
Class and exam questions
During this phase, mast cells degranulate, releasing histamine and other active substances, and the synthesis of eicosanoids begins.
During this phase, mast cells degranulate, releasing histamine and other active substances, and the synthesis of eicosanoids begins.
Yes, low-molecular-weight substances such as medications can become allergens if they bind to the body's proteins, acting as haptens.
Yes, low-molecular-weight substances such as medications can become allergens if they bind to the body's proteins, acting as haptens.
Allergy is based on a Th2-dependent humoral immune response, which results in the production of IgE class antibodies.
Allergy is based on a Th2-dependent humoral immune response, which results in the production of IgE class antibodies.
What else to study on this topic
- Experimental models of allergic reactions (Prausnitz–Küstner reaction, Passive cutaneous anaphylaxis, Schulz–Dale reaction)
- Molecular mechanisms of mast cell activation via FcεRI
- The role of eicosanoids in the pathogenesis of allergic reactions
- Mechanisms of Th2 cell formation and their functions
- Differences between natural and recombinant allergens
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